The amino acid sequence of several short peptides from the skin of Xenopus frogs had been determined by molecular cloning techniques. The peptides range in length from 21 to 35 amino acids. Although the peptides failed to show secondary structure in solution by NMR techniques, computerized secondary structure prediction techniques indicated that the peptides might form amphipathic helices. We modeled a series of helices and then formed the several helices into a cylinder. The cylinder of peptides we imagined would imbed itself in a membrane and form a channel. This was the essential insight. Several orientations of the helices were tried as well as several different sizes of cylinders. The protein assemblies with between six and eight helices seem to be most coherent when the helices are oriented in the same direction. Molecular energy calculations have been applied to these assemblies. The molecular modeling focused attention on the idea that the magainin peptides act to form channels in membranes. Patch clamp experiments have since shown that the peptides form channels at very low concentrations. The model predicts that the channels will accommodate negative ions which leads us to believe that the mode of action involves destabilizing the chloride pump in a cell. Physical testing of this hypothesis is proceeding. Molecular energy calculations with chloride ions is now in progress.